In sub-Saharan Africa, HIV-negative individuals in stable heterosexual relationships with HIV- positive individuals face a very high risk of HIV infection. Among those couples who want to have children, promoting abstinence and condoms may not be viable or acceptable options for reducing sexual HIV transmission risk. Antiretroviral treatment (ART) dramatically reduces the risk of sexual and perinatal HIV transmission. Recent exciting successes with vaginal microbicides and the promise of antiretroviral pre- exposure prophylaxis (PrEP) may offer additional protection against sexual transmission of HIV while allowing for conception. Understanding trends and predictors of fertility intentions, periconception behaviors, and pregnancy among HIV-affected couples is a critical step towards designing novel bio-behavioral reproductive counseling interventions to reduce sexual HIV transmission risk in the context of desired conception. Objectives We will examine the prevalence and predictors of fertility desire and reproductive behavior, and the incidence of pregnancy among HIV-positive women and men on ART who report HIV-negative partners. We will also explore attitudes towards biologic interventions to reduce sexual transmission during conception. Aims We aim to (1) Analyze longitudinal trends and predictors of fertility desire and behavior among ART- treated women and men with HIV-negative partners by key biological, behavioral, social, and structural predictors; (2) Measure incidence of pregnancy and livebirth among a) women on ART with HIV-negative partners and b) HIV-negative partners of men on ART; and (3) Explore acceptability of biologic interventions (microbicides, PrEP) for reducing sexual HIV risk while enabling conception among discordant couples. Methods We propose to add a Reproductive Health survey and pregnancy-testing module to the ongoing NIH-funded Ugandan Antiretroviral Treatment Outcomes (UARTO) cohort of 1000 ART-treated individuals in Mbarara, Uganda. Participants will complete an annual interview to assess fertility intentions, reproductive behaviors, and pregnancy. Women will also undergo quarterly -hcg urine testing; male participants will be asked to report incident pregnancies among sexual partner(s). Log-linear and survival analysis methods (with a generalized estimating equation extension) will be used to model predictors of the primary outcomes. Our work will be grounded in an ART-specific conceptual model of fertility change (adapted from Bongaarts' proximate determinants of fertility). Innovation With the advent of novel biologic strategies to reduce sexual HIV transmission, it is paramount to understand how these interventions apply to serodiscordant couples who desire children. This work will lay the foundation for the design of integrated bio-behavioral reproductive health interventions to reduce HIV transmission rates between serodiscordant partners and their infants. PUBLIC HEALTH RELEVANCE: In sub-Saharan Africa, HIV-negative individuals in stable heterosexual relationships with HIV-positive individuals face a very high risk of acquiring HIV. Promoting condoms and abstinence does not account for fertility desires, which are common among HIV-affected men and women. We aim to understand attitudes towards bio-behavioral strategies to reduce periconception HIV transmission risk as well as trends and predictors of fertility desire, behaviors, and pregnancy among HIV-affected couples in Uganda as a first step towards designing interventions to reduce sexual transmission of HIV in the setting of desired conception.